Mesoionic Imines (MIIs): Strong Donors and Versatile Ligands for Transition Metals and Main Group Substrates

Abstract We report the synthesis and the reactivity of 1,2,3‐triazolin‐5‐imine type mesoionic imines (MIIs). The MIIs are accessible by a base‐mediated cycloaddition between a substituted acetonitrile and an aromatic azide, methylation by established routes and subsequent deprotonation. C=O‐stretching frequencies in MII−CO2 and −Rh(CO)2Cl complexes were used to determine the overall donor strength. The MIIs are stronger donors than the N‐heterocyclic imines (NHIs). MIIs are excellent ligands for main group elements and transition metals in which they display substituent‐induced fluorine‐specific interactions and undergo C−H activation. DFT calculations gave insights into the frontier orbitals of the MIIs. The calculations predict a relatively small HOMO–LUMO gap compared to other related ligands. MIIs are potentially able to act as both π‐donor and π‐acceptor ligands. This report highlights the potential of MIIs to display exciting properties with a huge potential for future development.

Wavenumbers are reported in cm -1 . Mass spectrometry was performed on a microTOFQ Bruker Daltonics. Elemental analysis was performed on an Elementar VarioMICRO cube. X-ray diffractometry was carried out on either an Apex II Duo from Bruker with or a STADIVARI from STOE with molybdenum radiation (λKα = 0.71073 Å). Structures were solved by using SHELXL and refined using SHELXT. [7] 2. Synthesis Potassium butoxide (0.56 g, 5.02 mmol, 1.2 eq) and copper(I)-iodide were dissolved in DMSO (9 mL). The reaction vessel was placed into an ice-water bath and benzyl cyanide (0.49 g, 4.18 mmol, 1 eq) was added immediately dropwise. After complete addition 2,4,6trimethylphenylazide (0.81 g, 5.02 mmol, 1.2 eq) was added dropwise into the solution. The solution was stirred for another 15 minutes after complete addition while still submerged in icy water. The solution was allowed to warm up to room temperature and stirring was continued for 2 hours. The reaction was quenched by the addition of icy water (100 mL), while the product precipitated as an orange solid. The solid was filtered off and washed with generous amounts of water (3x 100 mL). The solid was dissolved in CH2Cl2 (20 mL) and washed with aqueous NH4OH-EDTA solution until the aqueous layer was colourless. The combined organic layers were dried (Na2SO4) and filtrated. The solvents were removed under reduced pressure yielding an orange oil. The crude product was dissolved in Et2O (5 mL). The addition of hexane resulted in the deposition of the product as a red oil. Decantation of the liquid and removing of volatiles on high vacuum yielded the desired product as an orange solid, which was used without further purification (1.69 mmol, 48%, 559 mg).  2,4,6-Trimethylphenylacetonitrile (1.05 g, 6.59 mmol, 1 eq) was submitted into an oven dried Schlenk flask. THF (50 mL) was added under a flow of argon and the solution was cooled to -40 °C. A solution of n-butyllithium in hexanes (2.64 mL, 2.5 M, 1 eq) was added dropwise to the stirring solution and the solution was stirred for 10 minutes. 2,4,6-Trimethylphenylazide was added dropwise into the solution and the solution was over night while slowly heating up to room temperature. The solution was slowly poured into icy water (150 mL) and stirred for another 30 minutes at room temperature until all ice melted. The solution was extracted with EtOAc (3x 100 mL).
The combined organic layers were washed with brine (2x 100 mL), dried (Na2SO4) and filtrated over a pad of wool. After removal of the solvent under reduced pressure the crude product was obtained as an orange oil. The oil was dissolved in the least amount of boiling ethanol (~ 10 mL) as possible. After the solution was allowed to cool to room temperature crystallisation was induced by adding a few seed crystals from an earlier batch. The vessel was placed into a freezer for 2-3 days (-20 °C) for quantitative crystallisation. The product was obtained after filtration and washing of the filter cake with ice-cold ethanol as colourless needles. Seed crystals could be obtained by placing the oversaturated ethanol-solution in the fridge (6 °C) for several days. (1.98 mmol, 42%, 0.80 g).
Single crystals suitable for X-ray diffractometry were obtained by slow diffusion of hexane into a saturated solution of the product in CH2Cl2 at room temperature over the course of several days.
According to a literature-known procedure [8] , the triazole 1d (307 mg, 1.29 mmol, 1 eq) and m-CPBA (380 mg, 2.59 mmol, 2 eq) were submitted to a roundbottom flask and dissolved in CHCl3 (20 mL). The solution was stirred under reflux for 30 minutes. The solution was allowed to cool to room temperature. The solution was washed with an aqueous Na2S2O3-solution. The organic layer was separated and the aqueous layer was extracted with CH2Cl2 (1x 20 mL). The combined organic layer were washed with aqueous NaOH-solution.
The organic layer was separated, dried (Na2SO4) and filtrated over a pad of wool. The volume was reduced to ~2 mL and the solution was overlayered with EtOH yielding orange single crystals suitable for X-ray diffractometry after several days. Further investigation of the thus obtained crystals by NMR shows that the crsystalline material does not appear to be a well-defined product ( Figure S7) General procedure for triazolium iodides 2a-c (GP I) According to a literature-known procedure [9] , the appropriate triazole 1a-c was submitted into an oven-dried Schlenk flask. MeCN and methyliodide were added under a flow of argon. The Schlenk flask was sealed with a stopcock and the mixture was heated to 60 °C.
The stopper was lifted to release pressure and the solution was stirred for 3 days at 60 °C in a sealed flask. After 3 days, the reaction mixture was allowed to cool to room temperature and volatiles were removed under reduced pressure.  Triazolium salt 2a (300 mg, 0.79 mmol, 1 eq) and potassium hexamethyldisilazide (158 mg, 0.79 mmol, 1 eq) were submitted into an oven-dried Schlenk flask and cooled to -78 °C. THF (30 mL) was added. The reaction mixture was stirred for 30 minutes, warmed to room temperature and then stirred for 1 hour at room temperature. Volatiles were removed under reduced pressure. The residue was suspended in toluene (10 mL) and filtrated over a pad of cellite. The filter cake was extracted with toluene (2x 10 mL). Removal of the solvent under reduced pressure yielded the product as a bright yellow solid (0.64 mmol, 81 %, 160 mg). Pure product was obtained after trituration of the product with small amounts of toluene.
Single crystals suitable for X-ray diffractometry were obtained by storage of a saturated solution of the product in benzene at 4 °C for several weeks.  Triazolium salt 2b (154 mg, 0.37 mmol, 1 eq) and potassium hexamethyldisilazide (73 mg, 0.37 mmol, 1 eq) were submitted into an oven-dried Schlenk flask and cooled to -78 °C. THF (10 mL) was added. The reaction mixture was stirred for 30 minutes, warmed to room temperature and then stirred for 1 hour at room temperature. Volatiles were removed under reduced pressure. The residue was suspended in Et2O (5 mL) and filtrated over cellite. The filtrate was discarded. The filter cake was extracted with toluene (3x 10 mL).
Removal of the solvent under reduced pressure yielded the product as an orange solid (0.21 mmol, 56 %, 60 mg).
Single crystals suitable for X-ray diffractometry were obtained by storage of a saturated solution of the product in toluene at -16 °C for several weeks. The obtained structure shows that 3b and 2b co-crystallised.      Preparation of 1d-O single crystals suitable for X-ray diffractometry According to a reported protocol [8] , a round-bottom flask was equipped with a stir bar, the triazole 1d (307 mg, 1.29 mmol, 1 eq) and mCPBA (580 mg, 2.59 mmol, 2 eq). Distilled chloroform (20 mL) was added and the solution was stirred under reflux for 30 Min. The solution was allowed to cool to room temperature. The organic phase was washed with aqueous Na2S2O3-solution, followed by washing with aqueous NaOH-solution. The combined aqueous layers were extracted with CH2Cl2 (2x 10 mL). The combined organic layers were dried (Na2SO4) and filtrated. A crude product mixture was obtained after removal of the solvent under reduced pressure as a highly viscous red oil. Single crystals were obtained after several days by over layering a concentration solution of the crude product in CH2Cl2 with EtOH at room temperature.
Ir I The ligand precursor 2a (18 mg, 0.05 mmol, 1 eq), NaOAc (23 mg, 0.29 mmol, 6 eq) and [Ir(Cp*)Cl2]2 (19 mg, 0.02 mmol, 0.5 eq) were submitted into an oven-dried Schlenk flask. Under a flow of argon, MeCN (6 mL) was added and the flask was sealed. The mixture was heated to 65 °C, the stop-cock was lifted to release pressure and the mixture was stirred at 65 °C in the sealed flask for three days.
The mixture was allowed to cool to room temperature. The suspension was filtered through a pad of cellite and the solvent in the filtrate was removed under reduced pressure. The residue was suspended in Et2O (10 mL) and sonicated with ultra-sound for 1 hour. The resulting red solid was filtrated and washed with small amounts of ice-cold Et2O. The product was obtained in a pure form as red needles after crystallisation through slow diffusion of n-pentane at room temperature into a concentrated solution of the crude product in CH2Cl2 over the course of several days (0.04 mmol, 75%, 25 mg).
Single crystals suitable for X-ray diffractometry were obtained the same way.  The ligand precursor 2b (28 mg, 0.07 mmol, 1 eq), NaOAc (33 mg, 0.40 mmol, 6 eq) and [Ir(Cp*)Cl2]2 (27 mg, 0.03 mmol, 0.5 eq) were submitted into an oven-dried Schlenk flask. Under a flow of argon, MeCN (6 mL) was added and the flask was sealed. The mixture was heated to 65 °C, the stop-cock was lifted to release pressure and the mixture was stirred at 65 °C in the sealed flask for three days.
The mixture was allowed to cool to room temperature. The suspension was filtered through cellite and the solvent in the filtrate was removed under reduced pressure. The residue was suspended in Et2O (10 mL) and sonicated with ultra-sound for 1 hour. The resulting red solid was filtrated and washed with small amounts of ice-cold Et2O. The product was obtained in a pure form as red plates after crystallisation through slow diffusion of n-pentane at room temperature into a concentrated solution of the crude product in CH2Cl2 over the course of several days (0.03 mmol, 40%, 20 mg).
Single crystals suitable for X-ray diffractometry were obtained the same way.  were submitted into an oven-dried Schlenk flask. Under a flow of argon, MeCN (15 mL) was added and the flask was sealed. The mixture was heated to 65 °C, the stop-cock was lifted to release pressure and the mixture was stirred at 65 °C in the sealed flask over night. The mixture was allowed to cool to room temperature. The suspension was filtered through cellite. The solvent in the filtrate was reduced to ~2 mL and the product obtained in a pure form after precipitation by addition of Et2O as an orange powder (0.17 mmol, 66%, 160 mg).
Single crystals suitable for X-ray diffractometry were obtained as red needles by slow diffusion of Et2O at room temperature into a concentrated solution of the product in MeCN over night.   Crystallisation by diffusion of either Et2O or n-pentane at room temperature into a concentrated solution of 5d-acetone in acetone over the course of several days yielded a pure product in the form of green plates. Single crystals suitable for X-ray diffractometry were obtained as green plates following the same procedure.  Single crystals suitable for X-ray diffractometry were obtained as yellow plates by slow diffusion of n-pentane at room temperature into a concentrated solution of the product in toluene over the course of several weeks. 3. NMR-spectra                                      The crystallographic data shows ( Table 1), that the relevant C1-N4 bond length is in the same range for the respective 1,4-diphenyl (1a-3a) and Compared to the triazolium salt 2a, the 1 H-NMR-spectrum of 3a shows one signal with an integral of 2 (relative to δ 1 H(N-CH3)) shifted to significantly higher frequencies while two distinct signals with a relative integral of 1 in each case are shifted towards lower frequencies ( Figure   S41). This behaviour is explained by the previously illustrated intramolecular interactions of the respective ortho-hydrogen atoms in the phenyl moieties with the exocyclic N-fragment. Breaking of the C2-symmetry in the phenyl substituents is a direct result of these interactions. Hence     The sample was then flushed with argon-gas for 10 minutes resulting in a bright yellow coloured solution. 1 H and 13 C-NMR-spectra were recorded again with this sample yielding the native spectrum of the first sample.
The ligand 3a (20 mg, 0.08 mmol, 1 eq) was submitted into an oven-dried Schlenk-flask. Under a flow of argon the ligand was dissolved in a mixture of toluene (3 mL) and n-pentane (3 mL). CO2-gas (1 bar) was bubbled through the solution for 1 hour. The formed precipitated was separated from the solution by transfer onto a frit via CO2-pressure and Teflon tubing. The filter cake was washed npentane (2x 3 mL) and then dried by a mild flow of CO2-Gas for 1 hour. IR-measurements of the solid with an ATR-unit were conducted immediately. The ligand 3a (16 mg, 0.06 mmol, 1 eq) and B(C6F5)3 (33 mg, 0.06 mmol, 1 eq) were submitted into an oven-dried Schlenk-flask and cooled to 0 °C. C6D6 (1 mL) was added under a flow of argon and the solution was stirred for 10 minutes. The solution was allowed to warm to room temperature and was stirred over night at room temperature. The resulting colourless solution was investigated.
Single crystals suitable for X-ray diffractometry were obtained by slow diffusion of hexane into a solution of 3a-B(C6F5)3 in toluene at room temperature of the course of several days. One set of signals can not be assigned as they collapse with the residual solvent signal.        Figure S50. Structure of reported acyclic imine-B(C6F5)3 adducts 6a-c. [10] 6.3 Crystallographic data of Ir half sandwich complexes     Linear regression of the resulting van't Hoff plots:

Computational details
All calculations were performed using the ORCA 4.2.1 program. [11] Geometry optimizations were carried out using the PBE0 functional [12] with def2-SVP basis sets [13] on all atoms, starting from the X-ray determined structures, except for the 3a-CO2 adduct. The optimized structures were used for single point and frequency calculations with the PBE0 functional and def2-TZVP basis sets. For complex 3a-B(C6F5)3, the optimized structure was employed in single-point (but not frecuency) calculations, using the PBE0 functional and def2-TZVP basis sets, in order to calculate the electron density difference between the full complex and its 3a and B(C6F5)3 fragments, according to a methodology previously reported by our group. [14] Implicit solvation by CH2Cl2 was taken into account using the SMD method [14] together with the CPCM model. [15] The resolution-of-the-identity (RI) approximation [16] with matching basis sets (def2/J), [17] as well as the RIJCOSX approximation (combination of RI and chain-of-spheres algorithm for exchange integrals) were used to reduce the time of calculations. The optimized structures were confirmed to be minima by the absence of imaginary vibrational frequencies. Orbital and electron density isosurfaces were plot with Chemcraft [18] .
Frontier orbitals for the studied molecules       Crystal data and structure refinement for the co-crystallised system 3b-2b Figure S70. X-ray solid-state structure of the co-crystallised system 3b-2b.